Intensive insulin treatment in individuals w/IDDM attenuates the neuroendocrine and lipolytic responses to acute exercise. Rigorous metabolic control significantly enhances exercise capacity and the cardiovascular and metabolic adaptations to endurance training in IDDM, compared to the blunted training response seen in conventionally treated IDDM. Intensive pharmacologic treatment w/sulfonylureas, but not w/metformin, blunts the neuroendocrine and lipolytic responses to acute exercise in NIDDM and contributes to the increased risk of exercise-induced hypoglycemia in sulfonylurea-treated NIDDM patients. Sulfonylureas and metformin exert differential effects on the energy cost of physical activity and/or fuel utilization patterns during exercise in intensively treated NIDDM patients. Compared w/metformin treatment, intensive treatment w/sulfonylureas reduces energy expenditure and/or decreases fat utilization during equivalent physical activity, contributing to the propensity for weight gain and increased adiposity in sulfonylurea-treated NIDDM patients.